26 research outputs found

    Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events.</p> <p>Conclusion</p> <p>On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.</p

    Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences

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    <p>Abstract</p> <p>Background</p> <p>Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue.</p> <p>Methods</p> <p>H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer.</p> <p>Results</p> <p>H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth.</p> <p>Conclusion</p> <p>These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.</p

    Addressing climate change with behavioral science: a global intervention tournament in 63 countries

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    Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

    Addressing climate change with behavioral science:A global intervention tournament in 63 countries

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    Le double, Identité empruntée dans l'impasse (le lien entre l'impasse relationnelle et le double en tant que suppléant à un deuil non élaboré)

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    Cette étude est une réflexion sur la relation triangulaire entre une impasse relationnelle, un deuil non élaboré et la notion psychanalytique du double. L'impasse place le sujet dans une situation de "tout ou rien", dont la signification s avère être une impossibilité d'accepter la perte, la séparation, et l'altérité. Nous présumons que le deuil non élaboré est la raison pour laquelle quelqu un s'engage dans l'impasse, tandis que le double joue le rôle de suppléant à ce deuil, jusqu'au moment ou il s'avère illusoire, face à l'impasse. Le double désigne tout ce qui fait référence à une dualité chez l'être humain. Il médiatise les tensions entre les contraires tels que dehors et dedans, extérieur et intérieur, présence et absence. Dans cette optique, il désigne à la fois le clivage et la complétude, et c'est pour cette raison que nous le proposons en tant que solution (vraie ou illusoire) de l'impasse. Nous le montrerons dans cinq œuvres de la littérature hébraïque.The present study is a reflection on the triangular relationship between a relational impasse, unresolved loss and the psychoanalytic notion of the double. The impasse creates an "all or nothing" situation, the significance of which appears to be the inability to accept the loss, separation and otherness. We assume that denied grief is the reason behind an individual entering an impasse, while the double substitutes this loss even to the point where it becomes illusory. The double refers to everything that pertains to duality in human experience. It mediates the tensions between opposites, both without and within, present and absent. In this context, it refers both to the split and the whole and it is for this the reason that we propose it as a solution (real or illusory) to the deadlock. This is demonstrated by way of five Hebrew literary works.ST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF
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